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OBJECTIVE To determine the extent of use of unlicensed and off label drugs in children in hospital in five European countries. DESIGN Prospective study of drugs administered to children in general paediatric medical wards over four weeks. SETTING Children's wards in five hospitals (one each in the United Kingdom, Sweden, Germany, Italy, and the(More)
The maturation of organ systems during fetal life and childhood exerts a profound effect on drug disposition. The maturation of drug-metabolising enzymes is probably the predominant factor accounting for age-associated changes in non-renal drug clearance. The group of drug-metabolising enzymes most studied are the cytochrome P450 (CYP) superfamily. The(More)
BACKGROUND Enzymes of the cytochrome P450 3A (CYP3A) family are responsible for the metabolism of >50% of currently prescribed drugs. CYP3A5 is expressed in a limited number of individuals. The absence of CYP3A5 expression in approximately 70% of Caucasians was recently correlated to a genetic polymorphism (CYP3A5*3). Because CYP3A5 may represent up to 50%(More)
UNLABELLED Omeprazole is frequently used to treat gastroesophageal reflux in infants and children despite the lack of age-specific pharmacokinetic and dosing information in the approved product labeling. To address this challenge, the authors examined the potential influence of development and cytochrome P450 2C19 (CYP2C19) genotype on omeprazole(More)
BACKGROUND Midazolam, a benzodiazepine, is finding expanded use in neonatal intensive care units. We studied the pharmacokinetics and metabolism of midazolam after a single intravenous dose in preterm infants. METHODS The pharmacokinetics of midazolam and its hydroxylated metabolite (1-OH-midazolam) after a single 0.1 mg/kg intravenous dose of midazolam(More)
The data guiding the dosing, efficacy and safety of medicines for children have lagged substantially as compared to the information available for adults. As a consequence, pediatricians faced with the prospect of confining their practice to medicines with adequate information have frequently resorted to prescribing medicines for unapproved uses (different(More)
The approach to paediatric drug dosing needs to be based on the physiological characteristics of the child and the pharmacokinetic parameters of the drug. This review summarises the current knowledge on developmental changes in absorption, distribution, metabolism and excretion and combines this knowledge with in vivo and in vitro pharmacokinetic data that(More)
During human development impressive changes in drug disposition occur. An important determinant of drug clearance is metabolism, something that is not only determined by ontogenic regulation but also by genetic processes which add to the variability of drug metabolism during different stages of childhood. Therefore, an understanding of the developmental(More)